Abstract
Thermoresponsive polymer-grafted surfaces provide a powerful, versatile platform for dynamically modulating interfacial properties in response to temperature, enabling facile control over bioadhesive processes such as protein adsorption and cell adhesion. The functionality of these systems arises from polymers that undergo temperature-dependent conformational changes in aqueous environments, transitioning from hydrated and extended chains below their lower critical solution temperature (LCST) to more collapsed, hydrophobic structures above it. When grafted to surfaces, this transition alters interfacial wettability, thereby influencing interactions with biomolecules and cells. Previous studies demonstrate that features of thermoresponsive polymer architecture can influence temperature-driven surface properties. However, much of the existing work focuses on a relatively limited set of architectural variables and primarily evaluates their effects through biological outcomes. Because the physicochemical surface properties themselves are often not systematically characterized, it remains difficult to directly link polymer architecture to changes in interfacial behavior. Resultingly, the mechanisms by which polymer design governs thermoresponsive surface properties remain incompletely understood, highlighting a substantial and largely unexplored design space for systematically tuning surface behavior through polymer architecture. This thesis addresses these challenges by a) developing synthetic strategies for surface-attachable thermoresponsive polymers, b) stabilizing reactive surface coatings, and c) understanding how polymer architecture, namely, surface attachment point density and chain length, governs surface behavior towards expanding the functionality of temperature-responsive platforms.
Chapter 2 details the synthesis of thermoresponsive polymers containing surface attachment functionality using reversible addition fragmentation-chain transfer (RAFT) polymerization, providing control over molecular weight, dispersity, and attachment point density. We show the synthesis of copolymers containing thermoresponsive di(ethylene glycol) methyl ether methacrylate (DEGMA) units with methacrylic acid (MAA) or methacrylic acid N-hydroxysuccinimide (NHSMA) for conjugation to amine-functionalized surfaces, and with aminoethylmethacrylate (AEMA) units for aldehyde-functionalized surfaces. Because the spatial distribution of functional monomers could impact polymer behavior, we evaluate the effect of RAFT chain transfer agent (CTA) identity on monomer incorporation. Copolymers prepared using trithiocarbonate and dithiobenzoate CTAs exhibited different monomer distributions, suggesting that CTA identity provides an additional handle for tuning copolymer architecture. These studies established a framework for synthesizing well-defined thermoresponsive polymers with tunable attachment site density and distribution for subsequent evaluation of how polymer architecture influences surface behavior.
Chapter 3 addresses instability issues of aminosilane-based surface coatings used to introduce reactive amine functionality to glass substrates. Although widely employed for surface modification, aminosilane layers can hydrolyze in physiologic environments, compromising their ability to support robust polymer grafting. We show that an intermediate composition of monopodal and dipodal silane increases the stability of amine coatings while maintaining available attachment sites for later conjugation. Further, we show that by using a difunctional aldehyde, hydrolytic stability could be enhanced while introducing surface aldehyde groups for conjugation to amine-bearing thermoresponsive copolymers. While we demonstrate the successful attachment of a thermoresponsive copolymer through Schiff base formation, these linkages proved to be hydrolytically unstable through the complete loss of thermoresponsive behavior after a 24 h incubation in phosphate buffered saline at physiologic temperature. However, the incorporation of a reductive amination step allowed retention of thermoresponsive behavior after the incubation period. These studies establish a framework for fabricating surfaces with stable functional groups that support robust and hydrolytically stable polymer coatings.
Finally, in Chapter 4, we explore the relationship between polymer architecture and thermoresponsive surface behavior. By systematically varying the attachment point density and chain length of grafted thermoresponsive copolymers, we evaluate how these parameters impact temperature-dependent surface wettability. We find that architectures promoting greater chain mobility (lower attachment point densities and longer chain lengths) enhance surface hydration below the LCST and produced greater changes in hydrophobicity between temperatures. Conversely, architectures that constrain chain mobility (higher attachment point densities and shorter chain lengths) reduce wettability below the LCST and minimized thermal responsiveness. These results demonstrate that polymer architecture can be strategically tuned to control surface wettability and temperature-dependent surface behavior, providing design principles for engineering responsive coatings with predictable interfacial properties.
Collectively, this thesis establishes synthetic and interfacial design principles for fabricating stable thermoresponsive polymer coatings with tunable surface behavior. By exploring the relationships between polymer structure, surface chemistry, and interfacial response, these studies reveal how specific polymer architectural parameters and surface chemistries influence temperature-dependent wettability. These findings show how thermoresponsive surfaces can be engineered to achieve predictable and controllable interfacial behavior, enabling the development of robust polymer coatings for use in applications requiring dynamic control of surface properties in biologically relevant environments.
